Obesity is a significant health problem leading to increased risk for diabetes and cardiovascular diseases. The control of body weight is a complex process that likely involves the interplay of numerous molecular mechanisms and neural circuits, many of them yet undefined. Recent research advances have highlighted the crucial role of brain circuitry in body weight regulation, but for every advance in this area new questions have risen. Our long-range goal is to determine the extent to which melanocortins and opioid peptides are functionally related to each other in the regulation of food intake. The objective of this application is to understand whether the melanocortin and opioid peptides affect consummatory behavior in a coordinated manner, affecting the rewarding aspects of food intake. The central hypothesis of the application is that there is a functional interaction between food intake mediated through the a-MSH/Mc4-R system and opioid-related reward pathways in the arcuate-paraventricular nucleus projection. The rationale for the proposed research is based on preliminary results produced in our laboratory, which indicate that a-MSH/MC4-R and opioid systems influence one another in the control of food intake. The significance for the proposed research is that information regarding the mechanism by which the melanocortins and the Mc4-R modulates feeding could eventually lead to the development of pharmacological agents to treat obesity and other eating disorders. Part b, do melanocortin agonist/antagonists affect the rewarding aspects of ingestive behavior? Part II: Determine the extent to which the melanocortin and opioid systems affect each other.Part III: To what extents do melanocortin and opiold-related feeding signals regulate the expression of the melanocortin receptors in the hypothalamus?